tbuckley/cabot-search huggingface dataset:
Metabolic complete responses (mCR) in patients with metastatic uveal melanoma (mUM) treated with image-guided injection (IGI) of PV-10.
Authors: Krysta McVay, Rahul Sheth, Ravi Murthy, Dan S. Gombos, Brett W. Carter, Priya Bhosale, Nourel hoda Tahon, Gener C Balmes, Ysabell M Coz, Edwina Washington, Dominic Rodrigues, Eric Andrew Wachter, Sapna Pradyuman Patel
Journal: Journal of Clinical Oncology (2022)

9543 Background: Traditional CT imaging can underestimate the degree of anti-cancer treatment effect due to reliance on morphological changes of visualized tumors. In contrast, PET imaging offers information on metabolic activity using a positron emitting radiolabeled agent (e.g. FDG) but is less sensitive to changes in tumor size. FDG-PET images acquired, co-registered, and superimposed on CT images (PET-CT) allow spatial detection of anti-cancer activity. Moreoever, FDG-PET-CT can provide information regarding anti-tumor immune responses in patients receiving immunotherapy. Rose bengal (PV-10) is a small molecule autolytic immunotherapy in development for metastatic disease. When administered by intralesional injection, PV-10 can produce immunogenic cell death and a T-cell mediated immune response against treatment-refractory and immunologically-cold tumors. Herein, we report the FDG-PET-CT imaging responses of 7 metastatic uveal melanoma (mUM) patients who received percutaneous image-guided injection (IGI) of PV-10 into hepatic tumors. Methods: The Phase 1 study is evaluating safety, tolerability, and efficacy of intralesional PV-10 in hepatic tumors. PV-10 is administered percutaneously via IGI into designated tumors ≤4.9 cm in diameter. Response is assessed at Day 28, then every 3 months, using CT/MRI or PET-CT. Patients with multiple tumors may receive further IGI of PV-10 after Day 28. Results: To date, 25 mUM patients with liver metastases have been treated; 16 patients received standard of care immune checkpoint inhibitor (ICI) during or post PV-10 treatment. Seven subjects had FDG-PET-CT imaging during the study (baseline 1, follow-up 6). Two follow-up FDG-PET-CTs were performed 1 and 3 years after PV-10 injection with intervening ICI, and another was 1.5 years after PV-10, without any follow-on treatment. Four patients experienced mCR in all metastatic sites, including extrahepatic metastasis. Conclusions: FDG-PET-CT shows that PV-10 is capable of inducing mCR in injected (adscopal) and non-injected (abscopal) lesions. This pattern of response is suggestive of immunogenic cell death in mUM patients with liver metastases. Clinical trial information: NCT00986661.
LINC-17. A single center retrospective analysis of pediatric intracranial choroid plexus carcinoma in Beijing
Authors: Miao Li, Yanling Sun, Shuxu Du, Jin Zhang, Wanshui Wu, Liming Sun
Journal: Neuro-Oncology (2022)

Abstract Objective: To explore the clinical characteristics and outcome in children with intracranial choroid plexus carcinoma in Beijing. Methods: We retrospectively analyzed 13 children with pathologically confirmed diagnosis of choroid plexus carcinoma between January 2017 and December 2021. They were treated with surgical resection followed by adjuvant therapies. Results: Male/female ratio=0.625(5:8). The median age at diagnosis was 1.2 years (range, 6 months to 9.8 years) with 9 cases &amp;lt; 3 years of age. Gross total resection was achieved in 12 cases (92.3%), and subtotal resection in 1 case. Seven patients received only adjuvant chemotherapy according to CPT-SIOP-2009 protocol, and 6 patients underwent radiotherapy with combined chemotherapy. Six patients developed a recurrence, and 4 cases died at last follow-up. Among 9 patients alive, 7 cases attained CR, 1 PR and 1 SD.The 5-year progression-free survival (PFS) and overall survival (OS) were (64.8±14.3) % and (68.4 ± 13.1) %, respectively. The survival of children treated under both irradiation and chemotherapy were higher than chemotherapy only (P&amp;lt;0.05). The cases &amp;lt; 3 years of age had worse survival than those ≥3 years (P&amp;lt;0.05), and the 4 cases died were all younger than 3 years old. Conclusions: Choroid plexus carcinoma is a rare and malignant brain tumor, and affects mainly younger children in our center. Surgical resection is the mainstream treatment. Adjuvant radiotherapy with combined chemotherapy and patients older than 3 years old tend to have better survival. Keywords: Choroid plexus carcinoma; Therapy; Survival.
Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease
Authors: Arthur Kastl, Wenjing Zong, Victoria M. Gershuni, Elliot S. Friedman, Ceylan Tanes, Adoma Boateng, William J. Mitchell, Kathleen O’Connor, Kyle Bittinger, Natalie A. Terry, Christina Bales, Lindsey Albenberg, Gary D. Wu
Journal: Gut Microbes (2022)

Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states.
When is neoadjuvant androgen deprivation therapy beneficial for highly aggressive prostate cancer before radical prostatectomy? Implications for multi-modal tailored approaches and trials design
Authors: F.M. Barletta, G. Gandaglia, S. Scuderi, M. De Angelis, L. Toneatto, L. Quarta, D. Robesti, D. Cannoletta, G.O. Cirulli, A. Stabile, V. Cucchiara, L. Nocera, D. Raggi, L. Marandino, A. Necchi, E. Mazzone, E. Zaffuto, P.I. Karakiewicz, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Improved laryngeal function after neoadjuvant therapy for advanced thyroid cancer: A potential outcome of interest for future clinical trials.
Authors: Amr Hesham Abdelhamid Ahmed, Amanda Silver Karcioglu, Zipei Feng, David C. Shonka, Ayaka J. Iwata, Maria E. Cabanillas, Lori J. Wirth, Mark E. Zafereo, Gregory W. Randolph
Journal: Journal of Clinical Oncology (2022)

e18030 Background: Advanced thyroid cancers can invade the recurrent Laryngeal Nerve (RLN) resulting in vocal cord paralysis (VCP). This can significantly impact the surgical strategy given the need to sacrifice the invaded RLN, the potential for bilateral VCP and tracheotomy. Methods: We retrospectively identified patients diagnosed with advanced thyroid carcinomas (of any histology) at 3 high-volume tertiary centers who met the following criteria: treated between 01/2017 and 12/2022, tested for driver/targetable somatic mutations, received targeted neoadjuvant therapy, underwent laryngoscopic exam to assess vocal cords (VC) functional status before, during and after neoadjuvant therapy, and underwent surgery. Results: We identified 6 patients who met the eligibility criteria. Mean age at diagnosis is 69. Five patients were diagnosed with anaplastic thyroid carcinoma, while 1 with papillary thyroid carcinoma. Somatic mutations were detected in BRAFV600E in 6 patients (100%), TERT promoter in 3 (50%) and in PIK3CA &amp; TP53 in 2 patients each (33%). Five patients received dabrafenib/trametinib &amp; 1 patient received lenvatinib. One patient received radiotherapy before neoadjuvant therapy. Baseline laryngoscopic exam detected 5 left-sided VCP and 1 right-sided VCP. After neoadjuvant therapy, 4 patients (67%) regained VC function after 3 months of therapy. By 13.5 months, all patients (100%) regained normal VC function, with a mean time-to-return of VC function of 5 months. The affected RLN could be surgically spared in 5 patients (83%). Conclusions: Use of neoadjuvant targeted therapy resulted in return of VC function in all patients after initially abnormal laryngeal exams, with 67% of patients showing return of function after 3 months. Additionally, neoadjuvant therapy resulted in tumor response sufficient to spare 5 RLNs from surgical resection (83%). Serial laryngoscopic exams during neoadjuvant therapy could guide surgical strategy, impact surgical timing, and provide an additional meaningful treatment outcome. VC function could be used as an endpoint in future neoadjuvant trials. Potential limitations include tertiary center referral bias and selection bias (patients who met eligibility criteria may have favorable trajectory, while patients with aggressive disease who didn’t respond to therapy were excluded). Clinical trials are undergoing to further validate our results. [Table: see text]
Association of Low and Intermediate Combined Positive Scores With Outcomes of Treatment With Pembrolizumab in Patients With Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Yao Yu, Kaveh Zakeri, Eric J. Sherman, Nancy Y. Lee
Journal: JAMA Oncology (2022)

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A prescription for the government: tackle child poverty to help address health inequalities
Authors: Camilla Kingdon
Journal: BMJ (2022)

While the package of financial support delivered by the UK chancellor Rishi Sunak last week gives many families room to breathe, it won't touch the sides of child poverty.The lifelong implications of growing up in poverty are significant, both for the individual and in costs to society.Clinicians want to help-that's why we work in healthcare-but there is no prescription we can ever give that will tackle child poverty.The government needs to make a choice, and that choice must be investing in childhood-the nation depends on it.
Updated analysis of the efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic <i>NTRK</i> fusion-positive (<i>NTRK</i>-fp) solid tumors.
Authors: Maciej Jerzy Krzakowski, Shun Lu, Sophie Cousin, Egbert F. Smit, Christoph Springfeld, Koichi Goto, Pilar Garrido, Christine H. Chung, Jessica Jiyeong Lin, Victoria J. Bray, Bethany Pitcher, Harald Zeuner, Siddhartha Patel, Walter Bordogna, Hans Gelderblom
Journal: Journal of Clinical Oncology (2022)

3099 Background: NTRK gene fusions, coding for chimeric TRK proteins, are oncogenic drivers in many solid tumors. In an integrated analysis of three phase 1/2 trials (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]), entrectinib, a potent CNS-active TRK inhibitor, showed durable systemic and intracranial responses in pts with NTRK-fp solid tumors. We report updated data from a larger cohort with longer follow-up (clinical cutoff 2 Aug 2021). Methods: Pts with locally advanced/metastatic NTRK-fp solid tumors and ≥12 months’ follow-up from first tumor assessment were efficacy evaluable. The safety cohort also included pts from TAPISTRY (NCT04589845). Tumor responses were assessed by blinded independent central review (BICR) per RECIST v1.1 at Week 4 and every 8 weeks thereafter. Primary endpoints: objective response rate (ORR) and duration of response (DoR). Progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR and safety were also assessed. Results: The efficacy-evaluable cohort comprised 150 adults (vs 121 previously) with 17 different solid tumor types. Median age was 58.5 years; 91% of pts had ECOG PS 0–1 and 37% had received ≥2 prior lines of therapy. Median survival follow-up was 30.6 months. ORR was 61.3% (n = 92/150; 95% CI: 53.1–69.2), including 25 complete responses. Responses were observed in all tumor types with n&gt;1 (Table). Median DoR, PFS and OS were 20.0 months (95% CI 13.2–31.1), 13.8 months (95% CI 10.1–20.0), and 37.1 months (95% CI 27.2–not estimable [NE]), respectively. In pts with and without investigator-assessed baseline CNS metastases (n = 31 / n = 119), ORR was 61.3% (95% CI 42.2–78.2) and 61.3% (95% CI 52.0–70.1) respectively. IC-ORR was 69.2% (n = 9/13) in pts with BICR-assessed measurable CNS metastases; median IC-DoR was 17.2 months (7.4–NE). In the safety population (N = 235: all treated pts), most treatment-related adverse events (TRAEs) were grade 1/2 and not serious; the most frequent were dysgeusia (36.6%), diarrhea (29.8%) and weight increase (28.5%). TRAEs led to dose interruption, reduction and discontinuation in 32.8%, 24.3% and 7.2% of pts, respectively. Conclusions: In this updated analysis, entrectinib continued to demonstrate deep and durable responses and was well tolerated in pts with NTRK-fp solid tumors with or without baseline CNS metastases. Clinical trial information: STARTRK-2 [NCT02568267]. [Table: see text]
Auxiliary diagnosis of periampullary carcinomas by comprehensive next-generation sequencing.
Authors: Lei Yin, Mingming Yuan, Xuefeng Xia, Wen-Long Yu
Journal: Journal of Clinical Oncology (2022)

e16221 Background: Periampullary carcinoma, originating from ampulla, head of pancreas, common bile duct and duodenum, is a group of highly heterogeneous tumors with similar clinical presentations and anatomical sites but totally different prognosis. This study aims to investigate the potential diagnostic value of molecular testing in patients with periampullary carcinomas. Methods: This study retrospectively recruited patients diagnosed with periampullary, common bile duct, head of pancreas and duodenum cancers whose tumor tissue or circulating free DNA samples were sent to perform parallel hybridization-based next-generation sequencing of cancer-related genes ranging from 59 to 1021. Differentiated mutated genes were compared between different cancers using Fisher’s exact test and p &lt; 0.05 was significant. Results: A total of 199 patients were enrolled in this molecular analysis, including 74 periampullary carcinomas, 43 duodenal cancers, 31 cancers of the common bile duct and 51 pancreatic head carcinomas. The top five most commonly mutated genes in these cancers were listed in the table. Fisher’s exact test suggested that ARID1A and LRP1B mutations were more frequently identified in duodenal cancer compared to periampullary cancer (p = 0.016 and 0.010, respectively). Compared to common bile duct carcinoma, periampullary cancer had more APC mutations and less ERBB3 mutations (p = 0.017 and 0.027, respectively). Strikingly, there was no APC mutation identified in pancreatic head cancer. Conclusions: Many common mutations were detected in periampullary, common bile duct, head of pancreas and duodenum cancers, such as TP53, KRAS and CDKN2A. However, APC mutation was not detected in pancreatic head carcinoma that is characterized by the worst prognosis. Genetic testing may facilitate distinguish the prognosis of periampullary carcinoma and assist in the differential diagnosis of pancreatic head carcinoma.[Table: see text]
Psychiatric comorbidities associated with granuloma annulare: A case-control study in the All of Us database
Authors: Tejas P. Joshi, Victoria Chen, Jen-Li Dong, Katelyn Golden, Alexander Iacobucci, Yuli Lim, Beatrice Morrow, Nasim Khalfe, Madeleine Duvic
Journal: Journal of the American Academy of Dermatology (2022)
Holmium Laser Enucleation of the Prostate (HoLEP) vs. Prostate Artery Embolization (PAE) in the treatment of Lower urinary tract symptoms (NCT04236687): Initial results of a Randomized Controlled Trial (RCT).
Authors: R. Bultó Gonzalvo, J. Sempere, G. Tovar, D. Salvador Hidalgo, M. Bernardello Ureta, J.J. Areal Calama, F. Agreda Castañeda
Journal: European Urology (2022)
Clinical characteristics and outcomes of extrapulmonary small cell cancer: A retrospective analysis of the SEER database.
Authors: Hafez Mohammad Abdullah, Moataz Ellithi, Mamoon Ahmed, Lina Ali, Mohammad Ali, Faiz Anwer
Journal: Journal of Clinical Oncology (2022)

e20616 Background: Extrapulmonary small cell cancer (EPSCC) accounts for only 5-10% of small cell carcinoma, with the rest consisting of small cell lung cancer (SCLC). The incidence of this entity has been rising due to better diagnosis, however it is not well described and data is limited. We performed a Surveillance, Epidemiology and End Results (SEER) database analysis to further characterize the biology and clinical aspects of this entity, in comparison to SCLC. Methods: The Surveillance, Epidemiology and End Results (SEER) 18 database was used to obtain data on age, gender, ethnicity, survival, and tumor characteristics of n = 9,712 US patients diagnosed with EPSCC between 2000-2018 and these were compared to n = 118,514 patients with SCLC diagnosed during the same period. Results: Among the EPSCC cohort 58.1 % were males while in the SCLC cohort 50.3% were males. Median age of diagnosis was 65.50 years for EPSCC and 66.81years for SCLC. Among the EPSCC patients, 75.9 % were Caucasians, 9.2 % were African-Americans, and 8.8% were Hispanics. Amongst SCLC patients, Caucasians made up 83.1% of the patients, while African-Americans made up 8.6% and Hispanics made up 4.5 % of the patients. Most common sites for EPSCC were urinary bladder (20.2%), prostate (7%), cervix uteri (6.2%), pancreas (4.5%), rectum (3%), and ovaries (2.6%). Median OS for EPSCC was 8 months (95% CI: 8 - 8), while median overall survival for SCLC was 7 month (95% CI: 7 - 7). Hazard ratio for death for EPSCC: 0.77 (95% CI: 0.75 - 0.79), p &lt; 0.001. The survival at 12 months, 24 months and 60 months was 36%, 22%, and 13 % for EPSCC and 29%, 13%, and 5% for SCLC. There were no significant gender or racial differences in overall survival (OS). Conclusions: EPSCC has better overall and 5-year survival as compared to SCLC. There are no significant differences in survival outcomes in EPSCC patients based on location of primary, gender or race.
Comparison of 3 PCR-based assays for microsatellite instability detection in formalin-fixed paraffin-embedded tissues of patients with colorectal cancer.
Authors: Jun Yang, Biao Zhang, Wenyan Guan, Xiaohong Pu, Shuying Miao, Zhiwen Fan, Lu He
Journal: Journal of Clinical Oncology (2022)

e15042 Background: Routine assessment of microsatellite instability (MSI) status in colorectal cancer (CRC) patients can help with initial screening for Lynch syndrome, prediction of tumor prognosis and selection of patients for immunotherapy. Immunohistochemistry (IHC) and PCR-based approaches represent the current clinical laboratory standard for the evaluation of MSI status. Both Bethesda and Promega marker panels have been used widely in the world and the Bethesda panel and the six mononucleotides panel (NR21/BAT25/NR24/NR27/MONO27/BAT26) have been approved by the National Medical Products Administration (NMPA) in China. The Idylla MSI Test, a fully automated system based on real-time PCR, which incorporates 7 novel MSI loci (ACVR2A/BTBD7/DIDO1/MRE11/RYR3/SEC31A/SULF2) can perform MSI analysis within 150min using 1-3 tissue slides. The aim of this study was to evaluate the performance of the three 3 PCR-based assays for MSI detection including Idylla MSI Test, Bethesda and that six mononucleotides panel. Methods: One hundred and fifty-three formalin-fixed paraffin-embedded (FFPE) tumor tissues from patients with CRC were collected and their MSI status were analyzed using 3 PCR-based assays, respectively, i.e. the Idylla MSI, “2B3D” NCI panel and the six mononucleotides panel. All samples were previously evaluated by IHC method. Results: In the all 153 patients, IHC identified 27 cases to be MMR-deficient (dMMR), and 126 to be MMR-proficient (pMMR). Using IHC as a reference, the Idylla MSI had a higher consistency that showed overall agreement, sensitivity and specificity as 93.46%, 92.89% and 93.65%, respectively, while the corresponding values of the six mononucleotides panel were 84.31%, 92.59% and 82.54% respectively, and the “2B3D” NCI panel showed a sensitivity of 92.16%, a specificity of 88.89% and an overall concordance of 92.86%. The PCR-based approaches identified 11 more MSI-H cases than IHC while 22 dMMR cases identified by IHC were detected by all the 3 assays, 2 dMMR by 2 assays, 1 dMMR by one assay only and 1 dMMR by neither assays above. Moreover, the Idylla MSI showed advantages in ease of use, turnaround time (TAT) and small dose of tissue input. Conclusions: Our findings support that the Idylla MSI assay provides a rapid, reliable, and ease-to-use solution to MSI detection in Chinese CRC patients with high sensitivity and specificity. The inconsistent cases between IHC and PCR-based approaches need a further analysis.